Amphotericin B lipid soluble formulations versus amphotericin B in cancer patients with neutropenia

Cochrane Database Syst Rev. 2014 Sep 4;2014(9):CD000969. doi: 10.1002/14651858.CD000969.pub2.

Abstract

Background: Patients with cancer who are treated with chemotherapy or receive a bone marrow transplant have an increased risk of acquiring fungal infections. Such infections can be life-threatening. Antifungal drugs are therefore often given prophylactically to such patients, or when they have a fever.

Objectives: To compare the benefits and harms of lipid soluble formulations of amphotericin B with conventional amphotericin B in cancer patients with neutropenia.

Search methods: We searched PubMed from 1966 to 7 July 2014 and the reference lists of identified articles.

Selection criteria: Randomised clinical trials comparing lipid soluble formulations of amphotericin B with conventional amphotericin B.

Data collection and analysis: The two review authors independently assessed trial eligibility and risk of bias and abstracted data.

Main results: We found 13 trials (1960 patients). Lipid-based amphotericin B was not more effective than conventional amphotericin B on mortality (relative risk (RR) 0.5; 95% confidence interval (CI) 0.64 to 1.14) but decreased invasive fungal infection (RR 0.65; 95% CI 0.44 to 0.97), nephrotoxicity defined as a 100% increase in serum creatinine (RR 0.45; 95% CI 0.37 to 0.54), and number of dropouts (RR 0.78; 95% CI 0.62 to 0.97).For the drug used in most patients, AmBisome (4 trials, 1214 patients), there was no significant difference in mortality (RR 0.77; 95% CI 0.54 to 1.10) whereas it tended to be more effective than conventional amphotericin B on invasive fungal infection (RR 0.63; 95% CI 0.39 to 1.01, P value 0.053).AmBisome, amphotericin B in Intralipid (6 trials, 379 patients), amphotericin B colloidal dispersion (ABCD) (2 trials, 262 patients), and amphotericin B lipid complex (ABLC) (1 trial, 105 patients) all decreased the occurrence of nephrotoxicity, but conventional amphotericin B was rarely administered under optimal circumstances.

Authors' conclusions: It is not clear whether there are any advantages of lipid-based formulations if conventional amphotericin B is administered under optimal circumstances, and their high cost prohibits routine use in most settings. There is a need for large trials comparing lipid-based formulations of amphotericin B with conventional amphotericin B given in the same dose, with routine premedication for prevention of infusion-related toxicity, and with supplementation with fluid, potassium, and magnesium for prevention of nephrotoxicity.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Review
  • Systematic Review

MeSH terms

  • Amphotericin B / chemistry
  • Amphotericin B / therapeutic use
  • Antifungal Agents / chemistry
  • Antifungal Agents / therapeutic use*
  • Chemistry, Pharmaceutical
  • Humans
  • Neoplasms / complications*
  • Neoplasms / mortality
  • Neutropenia / complications
  • Neutropenia / drug therapy*
  • Neutropenia / mortality
  • Randomized Controlled Trials as Topic

Substances

  • Antifungal Agents
  • liposomal amphotericin B
  • Amphotericin B